Detrimental Impact of Comorbid Mental Disorders in Chronic Thromboembolic Pulmonary Hypertension　- A Retrospective Observational Study.

Background: The relationship between the prognosis of patients with both chronic thromboembolic pulmonary hypertension (CTEPH) and a mental disorder (MD) remains unclear. Methods and Results: The study group comprised 157 patients with CTEPH who underwent right heart catheterization and were subdivided into 2 groups according to the presence of MDs: MD and non-MD. The patients with MDs were defined as those who had visited a psychiatrist and were under psychotropic drug treatment. The primary outcome was a composite of all-cause death and worsening of PH. The median follow-up period was 1,164 days. The incidence of the primary composite outcome was higher in the MD group than in the non-MD group (24.0% vs. 6.8%), whereas the all-cause mortality rate was comparable between groups (12.0% vs. 6.1%). The mean pulmonary arterial pressure, cardiac index, and pulmonary vascular resistance at baseline were all similar between groups. The Cox proportional hazards model indicated that MD was an independent risk factor for the primary composite outcome (hazard ratio, 2.990; 95% confidence interval, 1.034-8.642). Conclusions: In the present study, concomitant CTEPH and MD was significantly associated with a poor prognosis and such patients should be carefully followed.

Safe and successful transition from oral selexipag to subcutaneous treprostinil in a patient with idiopathic pulmonary arterial hypertension treated with triple combination therapy.

Some patients with pulmonary arterial hypertension (PAH) might undergo transition to parenteral prostacyclin analogs due to inadequate response to oral combination therapy. However, there is no consensus on how transition from oral selexipag to subcutaneous treprostinil should be performed. Herein, we report a 56-year-old woman diagnosed with idiopathic PAH that was treated with initial combination therapy (10 mg of macitentan, 40 mg of tadalafil, and 3.2 mg of selexipag daily). Mean pulmonary arterial pressure (PAP) improved from 63 to 39 mm Hg. Transition to parenteral prostacyclin analog was required because cardiac index was below 2.5 L/min/m2. The selexipag was tapered off while subcutaneous treprostinil was titrated up to 30 ng/kg/min over 19 days. Hemodynamic parameters were slightly better than those before the transition. The mean PAP improved to 32 mm Hg by further gradual increases of subcutaneous treprostinil up to 60 ng/kg/min. Therefore, the patient having idiopathic PAH with inadequate response to oral triple combination therapy experienced successful transition from selexipag to subcutaneous treprostinil. Hemodynamic parameters were slightly more improved at a dose of 30 ng/kg/min of subcutaneous treprostinil than at a dose of 3200 µg daily of selexipag in the midst of disease progression. Learning objectives: There is limited evidence for transition of pulmonary vasodilators, especially from oral selexipag to subcutaneous treprostinil. Detailed change in hemodynamic parameters before and after transition and the way of performing transition in patients with idiopathic pulmonary arterial hypertension with exacerbations despite treatment with oral triple combination therapy may provide useful information for better management in the clinical setting.

Right ventricular pressure overload related to residual thrombotic burden in patients 1 year after acute pulmonary embolism: From the Nagoya PE study.

INTRODUCTION: Residual pulmonary thrombus is an important factor affecting long-term prognosis after acute pulmonary embolism (PE). In this sub-analysis of the Nagoya PE study, we aimed to evaluate the relationship between residual thrombi detected by our refined computed tomography (CT) imaging protocol and the results of a multifaceted assessment of patients 1 year after acute PE. MATERIALS AND METHODS: The Nagoya PE study was a prospective observational study of patients diagnosed with acute PE. At 1 year, patients were evaluated multifacetedly, including by enhanced CT using our refined protocol. RESULTS AND CONCLUSION: Forty-three patients completed full testing at 1 year. Patients were divided into three groups according to the modified CT obstruction index (mCTOI): no pulmonary thrombus, low mCTOI, and high mCTOI. At baseline, left ventricular end-diastolic dimension and tricuspid regurgitation (TR) pressure gradient differed significantly across the three groups. At 1 year, patients with TR velocity > 2.8 m/s were found only in the high mCTOI group (P = .022). No difference was observed in symptoms, exercise tolerance, and quality of life score. Multivariate regression analysis revealed that TR velocity > 2.8 m/s (P = .001) and change in oxygen saturation during a 6-min walking test (P = .043) at 1 year were significantly related to mCTOI at 1 year. High thrombotic burden might be detected in patients with right ventricular pressure overload at diagnosis of acute PE or after 1 year. These patients should be carefully and multifacetedly assessed for potential chronic thromboembolic pulmonary disease or chronic thromboembolic pulmonary hypertension.

Inhaled iloprost induces long-term beneficial hemodynamic changes in patients with pulmonary arterial hypertension receiving combination therapy.

Inhaled iloprost is an established treatment for pulmonary arterial hypertension (PAH). However, the long-term hemodynamic changes that inhaled iloprost induces are unclear. Here, we retrospectively enrolled 18 patients with PAH who received inhaled iloprost as add-on to oral combination therapy from December 2016 to January 2021 at our institute in Japan. We then examined the changes in hemodynamic parameters induced by iloprost in these patients during right heart catheterization (RHC). To examine the long-term effects of iloprost, we repeated the RHC examination at follow-up (median time to follow-up, 8.5 months). During both catheterization procedures, iloprost was administered by using an I-neb AAD system (Philips NV). In a comparison of pre-inhalation values at the first and follow-up RHCs, inhaled iloprost significantly improved mean pulmonary artery pressure (mPAP; 39.9 ± 7.8 to 32.5 ± 7.2 mmHg, p = 0.016) and pulmonary vascular resistance (PVR; 588.5 ± 191.7 to 464.4 ± 188.5 dyn s cm-5, p = 0.047). During the follow-up RHC, in a comparison of the pre-inhalation and best recorded values out to 30 min after the end of iloprost inhalation, iloprost significantly decreased mPAP (32.5 ± 7.2 to 30.0 ± 6.6 mmHg, p = 0.007) and PVR (457.8 ± 181.4 to 386.2 ± 142.8 dyn s cm-5, p = 0.025) and significantly increased cardiac output (4.19 ± 0.91 to 4.64 ± 1.01 L/min, p = 0.035). Iloprost may have not only acute vasodilation effects but also long-term hemodynamic benefits in PAH patients receiving combination therapy.

Pulmonary tumor thrombotic microangiopathy with thrombus in pulmonary artery caused by diffuse sclerosing variant of thyroid papillary adenocarcinoma: A case report.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease associated with malignant tumors that progresses to pulmonary hypertension. Gastric cancer is the most common cause, followed by breast cancer and lung cancer, whereas PTTM due to thyroid cancer has not been reported. In addition to pulmonary obstruction by tumor embolism, tumor cells stimulate endothelial cells to release angiogenetic factors, which induce remodeling of pulmonary arteries and veins and lead to lymphatic obstruction. There is limited information on the relationship between thrombus and PTTM. We herein report an autopsy case with PTTM which was caused by diffuse sclerosing variant of thyroid papillary adenocarcinoma, in which differential diagnosis included the acute phase of chronic thromboembolic pulmonary hypertension.

Clinical value of the HATCH score for predicting adverse outcomes in patients with heart failure.

The HATCH score is employed as a risk assessment tool for atrial fibrillation (AF) development. However, the impact of the HATCH score on the long-term adverse outcomes in patients with acute heart failure (AHF) remains unknown. We investigated the clinical value of the HATCH score in patients with AHF. From a multicenter AHF registry, we retrospectively evaluated 1543 consecutive patients who required hospitalization owing to AHF (median age, 78 [69-85] years; 42.3% women) from January 2012 to December 2019. These patients were divided into five risk groups based on their HATCH score at admission (scores 0, 1, 2, 3, and 4-7). The correlation between the HATCH score and the composite outcome, including all-cause mortality and re-hospitalization due to HF, was analyzed using Kaplan-Meier and Cox proportional-hazard analyses. The median HATCH score was 2 [1-3], and the median age was 78 years (69-85 years). During the follow-up period (median, 16.8 months), the composite endpoint occurred in 691 patients (44.8%), including 416 (27%) patients who died (with 65 [4.2%] in-hospitalization deaths) and 455 (29.5%) patients requiring re-hospitalizations due to HF. The Kaplan-Meier analysis showed a significant increase in the composite endpoint with an increasing HATCH score (log-rank, p < 0.001). The multivariate Cox regression model revealed that the HATCH score was an independent predictor of the composite endpoint (hazard ratio [HR] 1.181; 95% confidence interval [CI]: 1.111-1.255; p < 0.001) with all-cause mortality (HR 1.153, 95% CI 1.065-1.249; p < 0.001) and re-hospitalizations due to HF (HR 1.21; 95% CI 1.124-1.303; p < 0.001) in patients with AHF, regardless of the presence or absence of AF, ejection fraction, and etiology. The HATCH score is an independent predictor of adverse outcomes in patients with AHF.

Usefulness of a refined computed tomography imaging method to assess the prevalence of residual pulmonary thrombi in patients 1 year after acute pulmonary embolism: The Nagoya PE study.

BACKGROUND: Post-pulmonary embolism (PE) syndrome is an important clinical condition that can affect the long-term prognosis after acute PE. OBJECTIVE: We aimed to evaluate the prevalence of residual pulmonary thrombi and the thrombotic burden 1 year after acute PE, by using our refined computed tomography (CT) imaging method. PATIENTS/METHODS: In this prospective study, patients diagnosed with acute PE were recruited and examinations were conducted at 1 month, 6 months, and 1 year. Especially at 1 year, patients were evaluated multifacetedly, including by laboratory tests, quality-of-life, 6-min walking test, and enhanced CT. RESULTS: Fifty-two patients were enrolled. Two patients (3.8%) developed chronic thromboembolic pulmonary hypertension. A total of 43 patients completed evaluation at 1 year, among whom (74%) had residual thrombi, with a median modified CT obstruction index (mCTOI) of 10.7%. In multivariate analysis, residual thrombi at 1 month was the only factor significantly related to residual thrombi at 1 year (odds ratio, 103.4; 95% confidence interval, 4.2-2542.1). The tricuspid regurgitation pressure gradient ≥60 mmHg and left ventricular end-diastolic dimension at diagnosis were significantly related to mCTOI at 1 year (ß = 0.367, P = .003; and ß = -0.435, P = .001, respectively). CONCLUSIONS: Using our improved CT imaging protocol, we found a high prevalence of residual thrombi 1 year after acute PE. Furthermore, right ventricular overload was related to the thrombotic burden. The long-term treatment strategy of acute PE could be modified to include precise CT imaging.

Clinical impact of heart rate change in patients with acute heart failure in the early phase.

AIMS: Patients with acute heart failure (AHF) often present with an increased heart rate (HR), and the HR changes dramatically after initial treatment for AHF. However, the HR change after admission and the relationship between HR change in the early phase and prognosis have not been fully elucidated. METHODS AND RESULTS: From a multicentre AHF registry, we retrospectively evaluated 1527 consecutive patients admitted with AHF. HR change (%) was calculated by [HR (at admission) - HR (24 h after admission)] × 100∕HR (at admission). The median HR change was 15.1% (range, 2.0-28.4%). The HR decreased most in the first 24 h and then gradually thereafter [admission: 98 (81-117) b.p.m., 24 h: 80 (70-92) b.p.m., 48 h: 78 (68-90) b.p.m., and 72 h: 77 (67-88) b.p.m.]. In Kaplan-Meier analysis, the cumulative event-free rates in the composite endpoint of death and rehospitalization due to AHF showed better according to larger HR change (P = 0.012, log rank). Cox proportional hazards analysis showed that HR change was a prognostic factor for composite endpoint adjusted by age and sex [hazard ratio, 0.995; 95% confidence interval (CI), 0.991-0.998; P = 0.006]. HR change was associated with outcome adjusted by age and sex in patients with sinus rhythm (hazard ratio, 0.993; 95% CI, 0.988-0.999; P = 0.015), but not in patients with atrial fibrillation (hazard ratio, 0.996; 95% CI, 0.990-1.002; P = 0.15). CONCLUSIONS: A decrease in HR in the first 24 h after admission indicates better prognosis in patients with AHF, although the prognostic influence may differ between patients with sinus rhythm and those with atrial fibrillation.

Prognostic Value of Delirium in Patients With Acute Heart Failure in the Intensive Care Unit.

BACKGROUND: Delirium is a common adverse event observed in patients admitted to the intensive care unit (ICU). However, the prognostic value of delirium and its determinants have not been thoroughly investigated in patients with acute heart failure (AHF). METHODS: We investigated 408 consecutive patients with AHF admitted to the ICU. Delirium was diagnosed by means of the Confusion Assessment Method for ICU tool and evaluated every 8 hours during the patients' ICU stays. RESULTS: Delirium occurred in 109 patients (26.7%), and the in-hospital mortality rate was significantly higher in patients with delirium (13.8% vs 2.3%; P < 0.001). Multivariate logistic regression analysis showed that delirium independently predicted in-hospital mortality (odds ratio [OR] 4.33, confidence interval [CI] 1.62-11.52; P = 0.003). Kaplan-Meier analysis showed that the 12-month mortality rate was significantly higher in patients with delirium compared with those without (log-rank test: P < 0.001), and Cox proportional hazards analysis showed that delirium remained an independent predictor of 12-month mortality (hazard ratio 2.19, 95% CI 1.49-3.25; P < 0.001). The incidence of delirium correlated with severity of heart failure as assessed by means of the Get With The Guidelines-Heart Failure risk score (chi-square test: P = 0.003). Age (OR 1.05, 95% CI 1.02-1.09; P = 0.003), nursing home residential status (OR 3.32, 95% CI 1.59-6.94; P = 0.001), and dementia (OR 5.32, 95% CI 2.83-10.00; P < 0.001) were independently associated with the development of delirium. CONCLUSIONS: Development of delirium during ICU stay is associated with short- and long-term mortality and is predicted by the severity of heart failure, nursing home residential, and dementia status.